The major object of this work is to determine the relationship between the deiodination of thyroxine (T4), its monodeiodinationto 3,5,3'-triiodothyronine (T3), and the physiological action of the hormones, using the rat pituitary gland as a model system. The characteristics of the deiodinating system will be assessed through extensive studies performed in vitro. The metabolism of both T4 and T3 and the extent of conversion of T4 to T3 will be studied. The influence of thyrotropin-releasing hormone (TRH) on the metabolism of T4 and T3 will be determined. A concomitant study of T4 action in the pituitary, as determined by suppression of TSH release, and T4 metabolism will be made. Pituitaries from normal, thyroidectomized and TSH-treated animals will be employed. The effect of adding compounds which prevent the suppressive action of T4 or interfere with its metabolism will be determined. In all studies, T4 and T3 metabolism and action will be studied from both the quanitative and qualitative standpoints.